Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Male F344 rats, 8 weeks of age, were given 16 intrarectal administrations of N-methyl-N-nitrosourea (NMU) at one of three dose levels over a period of 8 weeks. Five days after the final NMU instillation, rats were placed on one of three diets: chow with gelatin beadlets, chow with beadlets containing 0.024% 13-cis-retinoic acid, or chow and beadlets with 0.006% of the trimethylmethoxy phenyl analog of retinoic acid ethylamide. Groups of 20-40 rats were killed at 22-26 weeks after the first carcinogen treatment. The number of rats with colon carcinoma and the number of tumors per rat were dose related. In addition, "blind" histopathologic evaluation of four predesignate colon locations revealed a dose-related incidence of microscopic preinvasive and invasive colon carcinomas. The feeding of diets containing these two retinoids did not significantly alter the incidence of these parameters of carcinogenesis or the mean histopathologic score at predesignated colon locations for preinvasive or invasive neoplastic lesions. Over 90% of the colon neoplasms induced were invasive tubulopapillary adenocarcinomas. The diameters of the tumors correlated significantly with degrees of invasion of the colons. Only 1 tumor (a signet ring carcinoma) metastasized to the peritoneal cavity. Only 2 of 300 rats treated with NMU had tumors at sites other than the colon.
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PMID:Dose response to intrarectal administration of N-methyl-N-nitrosourea and histopathologic evaluation of the effect of two retinoids on colon lesions induced in rats. 65 Jul 11

We now keep HFRSV free WF-Osaka rats and ACI rats together in the separate three animal rooms (animal room 1, 2 and 3) and the incidence of colon carcinoma is still high on the WF-Osaka rats in animal room 1 with the high humidity. Two female ACI rats developed colon carcinomas in the ascending colon. The gross and the histological appearance of the colon carcinoma were completely the same as those of WF-Osaka rats. ACI and WF-Osaka rat strain together have been kept bred in neighborhood of each other in different racks in the identical animal room 1. To obtain HFRSV free ACI rat strain, Antecedents born by cesarean section of ACI female pregnant rat were foster-bred by WF-Osaka female nursing rat incidentally, and at the fourth mating generation after the start of foster-breeding, they developed colon carcinomas at the age of four months. Before five out of eight F1 hybrids by WF-Osaka cancer carrying female rat x male ACI rat had developed the same colon carcinoma, but none of F1 hybrids by the contrary mating had developed colon carcinomas in this same animal room 1. Animal room 1 and 2 where there was a high incidence of colon carcinomas, had happened to be kept moistened. However, after disinfection of these animal rooms, the animal room 2 and 3 occurred to be kept dried, and rats of WF-Osaka strain ceased to develop colon carcinomas in the animal room 2. Thereafter, animal room 2 and 3 were adjusted to be kept moistened again. Subsequently WF-Osaka rats in the animal room 2 began to have colon carcinomas in the ascending colon as before, but none of rats developed colon carcinomas in the animal room 3. Based on these findings, we consider that milk factor at the time of foster-breeding played an important role first and high moistened condition of the animal room resulted in promoting effect on colon carcinogenesis on ACI rats and WF-Osaka rats as well.
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PMID:Adenocarcinoma in the ascending colon of ACI strain rat foster bred by WF-Osaka female rat. 136 50

The distribution of O6-methylguanine-DNA methyltransferase (MGMT) activity in extracts of tumors from 74 patients was measured. The results demonstrated that there was considerable variation of MGMT activity in different human tumor tissues as well as in different individuals. The mean values (X +/- SD, pmol/mg of protein) in breast cancer, stomach cancer, small cell lung cancer, non-small cell lung cancer, renal cell carcinoma, esophageal carcinoma, brain tumors, colon carcinoma and malignant melanoma were 1.071 +/- 0.374 (9), 0.515 +/- 0.107 (5), 0.509 +/- 0.251 (5), 0.461 +/- 0.227 (24), 0.329 +/- 0.246 (5), 0.273 +/- 0.376 (5), 0.244 +/- 0.175 (14), 0.242 +/- 0.308 (5) and 0.201 +/- 0.161 (2) respectively. It was notable that six samples (1/24 non-small cell lung cancer, 3/5 esophageal carcinoma, 1/14 brain tumors and 1/5 colon carcinoma) did not have any detectable level of MGMT activity. Activity of glutamine pyruvic transaminase (GPT) was also measured in the same extracts used for the assay of MGMT activity. The activity of GPT in these samples with undetectable level of MGMT activity was similar to those with significant MGMT activity. These results further strengthen the assumption that a certain fraction of human tumors are Mer-.
Carcinogenesis 1992 Sep
PMID:O6-methylguanine-DNA methyltransferase activity in human tumors. 139 31

Glucocorticoid hormones are thought to play a role in carcinogenesis as they regulate cell differentiation and proliferation. We have investigated the effect of dexamethasone on two cell lines derived from a colon carcinoma, which differ by their tumorigenicity. Dexamethasone was found to inhibit growth of both the progressive (PROb) and the regressive clone (REGb). Upon glucocorticoid treatment, PROb cells were found to secrete an additional Mr approximately 40,000 protein. The synthesis and the release in the culture medium of this protein is stimulated specifically by glucocorticoid agonists, and not by other steroid hormones. The anti-glucocorticoid RU 38486 is inefficient and suppresses the induction of this protein by dexamethasone. Induction is sensitive to actinomycin D, suggesting that regulation may be related to an alteration of the rate of mRNA synthesis. The cellular effect of glucocorticoid hormones being mediated through a specific soluble receptor, we have characterized this protein. The PROb cells contained more specific glucocorticoid-binding sites (approximately 170,000 sites per cell) than the regressive ones (REGb cells; approximately 100,000 sites per cell). In both clones, the receptor was associated with the Mr approximately 90,000 heat shock protein to yield large complexes (Stokes radius Rs approximately 7.5 nm), which were dissociated to the same extent upon heat- and salt-treatment. The steroid- and DNA-binding unit of the receptor, characterized under denaturing conditions using an anti-receptor monoclonal antibody, was found to be more degraded in the PROb cell line.
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PMID:Biological effects of glucocorticoid hormones on two rat colon adenocarcinoma cell lines. 156 48

Short chain (C2-C6) fatty acids are produced in the colon through bacterial fermentation of mainly dietary fibre. Butyrate (C4) possesses antineoplastic effects on human colon carcinoma cells, and epidemiological studies indicate that high fibre diets may reduce the incidence of colorectal cancer. The role of dietary fibre during colorectal carcinogenesis might therefore be related to its fermentation to butyrate. Faecal concentrations of total short chain fatty acids and concentrations and ratios of the individual C2-C6 fatty acids did not differ between 16 healthy controls, 17 patients with colonic adenomas, and 17 patients with colonic cancer. Comparison of the molar production velocities (mmol/l.hour) of total and individual short chain fatty acids from glucose, ispagula, wheat bran, and albumin in six and 24 hour faecal incubations showed no differences. The ratio of butyrate production to total short chain fatty acid production from fibre, however, was reduced in patients with colonic cancer and adenomas compared with healthy controls (ispagula, six hours: 6.4, 7.6, and 11.5% respectively, p = 0.005 and 24 hour: 9.1, 9.9, and 15.4%, p = 0.002; wheat bran, six hours: 9.9, 10.2, and 14.7% respectively, p = 0.06 and 24 hours: 15.1, 16.8, and 21.0%, p = 0.01). It may be that the low ratios of colonic butyrate formation combined with low fibre diets increase the risk of colonic neoplasia.
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PMID:Colonic fermentation of dietary fibre to short chain fatty acids in patients with adenomatous polyps and colonic cancer. 165 78

Development of colon carcinomas can be associated with allelic deletions on several chromosomes, including 5q and 18q. The APC gene on 5q and the DCC gene on 18q have been identified as potential tumour suppressor genes, whose suppression contributes to colon carcinogenesis. To investigate the role of genes in these deleted regions, we have now introduced a single normal human chromosome into a human colon carcinoma cell line, COKFu, through microcell hybridization. Several clones of hybrid cells containing normal chromosome 5, and others containing normal chromosome 18, were obtained. The morphology of the hybrid cells was markedly altered: the hybrids with chromosome 5 exhibited a closely packed polygonal morphology, and the hybrid cells with chromosome 18 were flattened. The cloning efficiency of the hybrid cells in soft agar was reduced from 0.46 to 0% of that of the parental carcinoma cells, and the tumorigenicity of these hybrid cells in athymic nude mice was completely suppressed. The growth properties of the hybrid cells with chromosome 11 were not substantially changed. These results strongly suggest that the genes on normal chromosome 5 and 18 function as tumour suppressors in colon carcinogenesis.
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PMID:Suppression of tumorigenicity in human colon carcinoma cells by introduction of normal chromosome 5 or 18. 167 Sep 65

Jejunoileal bypass (JIB) has been a widespread operation for treatment of morbid obesity. Bile acids are regarded as cofactors in the carcinogenesis of the colon, and, since intestinal bypass involves increased exposure of bile acids to the large intestinal mucosa, JIB has been postulated to increase the risk for colorectal carcinoma. In experimental studies on animals, the results have indicated an increased frequency of induced carcinomas, but in clinical series only one patient with colon carcinoma has been reported. Thirty women, operated on with JIB 11 to 17 years earlier, were examined by colonoscopy with multiple biopsies, systematically taken for histologic evaluation and flow cytometric DNA analysis. In only one patient, low-grade dysplasia was detected in an initial adenomatous lesion but was not visible macroscopically. No DNA aneuploidy was found. In a control group of 11 patients examined for non-neoplastic disease, neither dysplasia nor aneuploidy was diagnosed. Within 17 years postoperatively, we have, by these methods, not been able to verify any colorectal malignant transformation in patients operated on with JIB. However, since carcinogenesis is a long process, further surveillance will be demanded before an increased risk for colorectal carcinoma can be excluded.
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PMID:Colorectal cancer risk after jejunoileal bypass: dysplasia and DNA content in longtime follow-up of patients operated on for morbid obesity. 174 70

A quantitative overview of 14 studies of rat colon carcinogenesis was undertaken to examine the relationship between fat intake, and fat intake by degree of saturation, on the incidence of colon carcinoma while controlling for calorie consumption. Calorie consumption was not recorded in 11 of the 14 studies. Hence, two types of analyses were conducted. The first examines carcinoma incidence as a function of percent fat (by weight), with calories controlled for by including weight gain per week in the analysis. The second estimates calories per day, for studies not providing such information, using weight gain per week and age at death, followed by a joint analysis of estimated fat calories and estimated total calories. With either approach, a rather strong positive relationship between colon carcinoma incidence and fat intake is indicated for Fischer 344 rats, but no association is apparent for Sprague-Dawley rats. This situation is somewhat clarified when the degree of saturation is taken into account: both strains gave results that suggest a negative relationship between colon cancer incidence and omega-3 fatty acids intake and a positive relationship with non-omega-3 polyunsaturated fat intake among Fischer 344 rats. These analyses suggest an important and specific role for dietary fat in the promotion of rat colon carcinoma.
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PMID:Quantitative review of studies of dietary fat and rat colon carcinoma. 186 11

Since the 1960s, the loss of sulfomucin from colonic epithelium has been considered to be an indicator of an early stage of carcinogenesis; yet, the biochemical basis for this phenomenon has never been elucidated. We recently prepared a monoclonal antibody (mAb) 91.9H that immunoprecipitates the normal colonic mucins metabolically incorporating [35S]-sulfate. This mouse IgG1 antibody did not cross-react with colon carcinoma mucins that lack sulfate groups. Using normal colonic epithelia unlabeled or radiolabeled with [35S]sulfate and [3H]glucosamine, we purified a high molecular weight glycoprotein that reacts with mAb 91.9H. This was achieved by a combination of DEAE-cellulose anion-exchange chromatography, consecutive treatments with chondroitinase ABC plus heparitinase and with sodium dodecyl sulfate plus 2-mercaptoethanol, and gel filtration on Sepharose CL-2B in the presence of 8 M urea. Antibody reactivity was found in acidic but not neutral high molecular weight glycoproteins. After Sepharose CL-2B fractionation, the mAb 91.9H-reactive fractions consisted of a component with an approximate molecular weight of 500,000-900,000. A purified sulfomucin contained protein, neutral sugar, amino sugar, sialic acid, and sulfate in an approximate ratio of 2.5:1.0:1.1:0.4:0.5. The polypeptide portion was rich in hydrophilic amino acids, particularly threonine. Binding of mAb 91.9H in solid-phase assays was inhibited to 50% by purified normal colon acidic mucin at doses of 5-50 micrograms/ml, depending on different preparations. Various glycosaminoglycans or sulfatides did not show inhibitory activity. Sulfomucin reactivity with mAb 91.9H, as determined by solid-phase-binding inhibition and by dot blot assays, was significantly reduced by chemical desulfation of sulfomucins with anhydrous hydrochloric acid, suggesting that sulfate groups served as a portion of the immunochemical determinant for this antibody. Sulfate residues were apparently linked to alkaline-sensitive carbohydrate chains, but alkaline-released carbohydrate chains did not react with mAb 91.9H. Immunohistochemical examinations showed that mAb 91.9H bound normal colonic epithelial cells, which also stained with high-iron diamine, more strongly than it bound colon carcinoma cells.
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PMID:Human colonic sulfomucin identified by a specific monoclonal antibody. 191 91

Glucocorticoid hormones are thought to play a role in carcinogenesis, as they regulate cell differentiation and proliferation. We have previously shown that dexamethasone inhibits the growth of a rat colon carcinoma cell line, and induces the secretion of an Mr approximately 40,000 protein. We now report that the synthesis and the release in the culture medium of this protein is stimulated specifically by glucocorticoid agonists, and not by other steroid hormones. The anti-glucocorticoid RU 38486 is inefficient and suppresses the induction of this protein by dexamethasone. Induction is sensitive to actinomycin D, suggesting that regulation may be exerted by altering the rate of mRNA synthesis. Characterization of culture medium from dexamethasone-treated cells revealed that the Mr approximately 40,000 protein is glycosylated, and can be further separated from other secreted proteins by high-performance anion-exchange chromatography.
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PMID:A secreted Mr approximately 40,000 glycoprotein specifically induced by glucocorticoids in a rat colon carcinoma cell line. 207 Dec 35


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